Individuals infected with HIV are well known to develop both infectious retinopathies (e.g., Cytomegalovirus Retinitis) and non-infectious retinopathies (e.g., retinal microvascular occlusions such as cotton wool spots). In the era of HAART, these problems still occur and manifest in tests of vision function, as well as by ophthalmologic examinations, and in the case of infectious CMV retinitis, may still result in severe vision loss and blindness due to resistant CMV retinitis in patients who are not responding well to, or who cannot reliably take, HAART therapy. Infectious retinitis and low CD4 counts, which predispose to non-infectious retinopathy, are more common in minority groups. This grant uses new technologies and novel methods to achieve three related goals. The first goal is to determine the prevalence and severity of the visual dysfunction that we have observed in HAART era HIV patients that are free of infectious retinitis. This work will be done through a longitudinal observational study that will employ a variety of non and minimally invasive vision testing methods, including new types of visual field tests and the multifocal ERG, which can accurately measure the location of retina! signals generated during the vision process. Second, we have shown that retinal cotton wool spots, which cause permanent retinal and visual defects, form even in patients on HAART. We hypothesize that the cumulative effect of these lesions, together with other areas of retinal vessel damage, leads to widespread retinal changes that account for the visual field loss we have shown. We will study retinal cotton wool spots obtained from autopsy eyes through our collaboration with the California NeuroAIDS Tissue Network (CNTN). Such studies will employ new, highly sensitive and specific molecular methods such as TAQMan PCR to determine the molecular basis of these lesions. Third, we wish to further our work on local anti-CMV treatments and to pursue our new discovery: Namely, the ability to crystallize nucleoside and nucleotide analogues with potent high anti-CMV activity. Injection of such crystals into eyes with CMV retinitis will result in slow dissolution of these crystals and an extremely long acting injectable anti-CMV drug preparation.